RESUMEN
Aspergillus fumigatus is a ubiquitous opportunistic fungal pathogen that can cause aspergillosis in humans. Over the last decade there have been increasing global reports of treatment failure due to triazole resistance. An emerging hypothesis states that agricultural triazole fungicide use causes clinical triazole resistance. Here we test this hypothesis in Hamilton, Ontario, Canada, by examining a total of 195 agricultural, urban, and clinical isolates using 9 highly polymorphic microsatellite markers. For each isolate, the in vitro susceptibilities to itraconazole and voriconazole, 2 triazole drugs commonly used in the management of patients, were also determined. Our analyses suggested frequent gene flow among the agricultural, urban environmental, and clinical populations of A. fumigatus and found evidence for widespread sexual recombination within and among the different populations. Interestingly, all 195 isolates analyzed in this study were susceptible to both triazoles tested. However, compared with the urban population, agricultural and clinical populations showed significantly reduced susceptibility to itraconazole and voriconazole, consistent with ecological niche-specific selective pressures on A. fumigatus populations in Hamilton. Frequent gene flow and genetic recombination among these populations suggest greater attention should be paid to monitor A. fumigatus populations in Hamilton and other similar jurisdictions.
Asunto(s)
Antifúngicos/farmacología , Aspergillus fumigatus/efectos de los fármacos , Farmacorresistencia Fúngica/genética , Proteínas Fúngicas/genética , Fungicidas Industriales/farmacología , Flujo Génico , Humanos , Pruebas de Sensibilidad Microbiana , Repeticiones de Microsatélite/genética , Ontario , Recombinación Genética , Selección Genética , Triazoles/farmacologíaRESUMEN
OBJECTIVE: Previous studies combining biologic disease-modifying antirheumatic drugs (bDMARD) to treat rheumatoid arthritis (RA) have shown an increased risk of infection. However, the risk of infection with concurrent use of denosumab, a biologic agent for the treatment of osteoporosis, and a bDMARD remains unclear. Here, we evaluated the incidence of serious and opportunistic infections in patients treated concurrently with denosumab and a bDMARD and patients treated with a bDMARD alone. METHODS: A chart review of patients with RA from 2 Canadian rheumatology practices between July 1, 2010, and July 31, 2014, identified 2 groups of patients: those taking denosumab and a bDMARD concurrently (concurrent group) and those taking only a bDMARD (biologic-alone group). Patients were followed from the time of initiation of denosumab, or a matched index date for the biologic-alone group, to the end of the study or loss to followup. Instances of serious or opportunistic infections were recorded. RESULTS: A total of 308 patients (n = 102 for the concurrent group and n = 206 for the biologic-alone group) were evaluated. Within the concurrent group, 3 serious infection events occurred. Within the biologic-alone group, 4 serious infection events and 1 opportunistic infection event occurred. In both groups, all patients with serious or opportunistic infection recovered, and there were no instances of death during the study period. CONCLUSION: This study demonstrated a low occurrence of serious and opportunistic infections in patients with RA taking bDMARD, including patients with concurrent denosumab use.
